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Chloride is an essential element in the blood that plays important roles in acid and electrolyte balance, kidney and muscle function, and transport of minerals, water, and gases. Both high and low blood chloride levels can cause health issues. Keep reading to learn more about chloride, the disorders caused by changes in its concentration, and how to resolve them.

What is Chloride (Cl-)?

Chloride is an essential electrolyte (a mineral that conducts electricity when in water). Chloride is the body’s main anion (negatively charged electrolyte) and represents 70% of the total negative electrolytes [R, R].

Chloride is mainly excreted through the kidneys into the urine (although 99.1% is reabsorbed), dependent on the body requirements and chloride intake [R, R].

What Is the Chloride Blood Test?

Chloride levels are usually measured with a blood test, which is done as part of an electrolyte or metabolic panel. It can also be measured via sweat, serum, urine, and feces, in certain circumstances. The test measures the concentration of free chloride and the results are shown in milliequivalents of chloride per liter of blood (mEq/L) [R, R, R].

Normal Chloride Levels

Low chloride levels (<95-100 mEq/L) are referred to as hypochloremia, while high levels (>106-110 mEq/L) are known as hyperchloremia. It is important to note that certain conditions can interfere with the analyses and result in artificially high or low chloride levels [R].

For instance, if the blood contains excess solid material (excess triglycerides or plasma cell cancer), it can interfere with the electrode, incorrectly registering as lower chloride levels [R, R].

Conversely, electrolytes like iodide and bromide or drugs like salicylate can be incorrectly picked up by the electrode and register as higher chloride levels (such as in case of poisoning) [R, R, R].

Only sodium, potassium, chloride, and bicarbonate are normally measured in blood tests. The difference between non-measured negative and positive electrolytes is called “anion gap” and is used for quality control, and to diagnose acid-base disorders, excess of antibodies in the blood (paraproteinemia), and poisoning with lithium, bromide, and iodide [R, R, R, R, R].

Normal concentrations of the main electrolytes inside the cells (left) and in blood (right). Source: [R].

4) Metabolic Alkalosis

The loss of a positively charged electrolyte (hydrogen) and/or buildup of a negatively charged electrolyte (bicarbonate) promote the elimination of chloride to balance positive and negative charges [R, R].

Infusion or intake of high volumes of sodium bicarbonate causes blood alkalosis and may lead to chloride being exchanged for bicarbonate to maintain blood neutrality [R].

5) Electrolyte Imbalance

Because the blood concentration of positively charged electrolytes must equal that of negatively charged electrolytes, conditions that cause the loss of sodium and potassium often result in low blood chloride levels [R].

Consequences of Low Chloride Levels

1) Low Chloride Levels and Death Rate

A relationship betweenlow blood chloride levels and increased death rate has been demonstrated in several studies:

Ways to Increase Blood Chloride

1) Reducing the Intake of Certain Drugs

2) Treatment With Certain Drugs

Note: By writing this section, we are not recommending these drugs. We are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.

Low blood chloride levels and metabolic alkalosis can be treated with the following drugs:

2) Excessive Salt Intake

Excessive salt intake (salty food, infusion of 0.9% salt solution during patient resuscitation, or unintentionally swallowing salty water) exceeds the capacity of the kidneys to excrete sodium and chloride, and increases water loss from urination and diarrhea, leading to a buildup of both electrolytes [R, R, R].

3) Metabolic Acidosis

Metabolic acidosis (low blood pH) occurs when the body produces excessive acids or insufficient bicarbonate. This loss of bicarbonate increases the concentration of chloride to maintain negative charges in the blood [R, R].

Alternatively, some forms of diarrhea cause the excretion of bicarbonate, which increases the retention of chloride [R].

Chloride buildup linked to metabolic acidosis also occurs in a condition in which the kidneys fail to absorb bicarbonate (proximal kidney tubular acidosis) or in patients suffering from chronic kidney failure [R, R].

4) Electrolyte Imbalances

Positive and negative charges in the blood must be balanced to remain electrically neutral. Conditions promoting the increased buildup of positive electrolytes such as sodium and potassium in the blood will lead to the excessive accumulation of chloride [R].

Consequences of High Chloride Levels

1) High Chloride Levels and Kidney Function

Several studies found a link between high blood chloride levels and increased incidence of kidney injury:

A retrospective cohort study and a DB-RCT on 1,045 and 2,278 critically ill patients [R, R]

In an observational retrospective study on 213 patients who underwent kidney transplantation, no positive correlation could be found between high blood chloride levels in the donor and the incidence of acute kidney injury in the recipient [R].

Infusion of 0.9% salt solution reduced blood flow in the kidneys as a result of high blood chloride levels (DB-RCT on 12 healthy volunteers) [R].

2) High Chloride Levels and Death Rate

A relationship between high blood chloride levels and increased death rate of critically ill patients has been demonstrated in these studies:

3) High Chloride Levels and Blood Circulation

In two studies, patients infused with 0.9% salt required higher volumes of a neurotransmitter (catecholamine) to increase their blood pressure and support circulation than those infused with a balanced solution (RCT on 150 patients undergoing kidney transplantation and DB-RCT of 60 patients undergoing major stomach and bowel surgery) [R, R].

In a study, the infusion with a balanced solution (Ringer’s lactate) instead of 0.9% salt reduced blood loss during the operation (DB-RCT on 66 patients undergoing aortic reconstruction surgery) [R].

4) High Chloride Levels and Stomach Function

In a study (DB-RCT) on 47 elderly patients, infusion with 0.9% salt caused reduced blood flow through the stomach lining and increased nausea and vomiting when compared to balanced solutions (Hartmann’s and Hextend) [R].

In a trial (SB-RCT on 18 healthy volunteers) infusion with 0.9% salt caused a higher incidence of stomach discomfort than with a balanced solution (Ringer’s lactate) [R].

5) High Chloride Levels and Immune System

High blood chloride concentrations increased the circulating cytokine levels in a study in rats with septic shock but failed to do so in a similar experiment [R, R].

In two cell studies, exposure to a chloride-concentrated solution reduced the activation and attachment to the inner blood vessel lining of white blood cells, suggesting that infusion with high-chloride fluids reduces the risk of septic shock [R, R].

6) High Chloride Levels and In-Hospital Complications

In a meta-analysis of 21 studies involving 6,253 critically ill patients, infusion with high-chloride fluids was associated with the requirement for longer mechanical ventilation times [R].

In two cohort studies (one on 31,920 patients undergoing surgery and one on 3,166 patients with systemic inflammatory syndrome), infusion with 0.9% salt increased the incidence of infections after the operation [R, R].

Genetics of Blood Chloride Levels

The following genetic conditions are associated with abnormal chloride levels.

1) Gordon’s Syndrome

Pseudohypoaldosteronism type II (PHAII), also known as Gordon’s syndrome, is a rare hereditary disease characterized by high blood chloride levels [R].

In the kidneys, the proteins WNK1 and WNK4 activate the electrolyte transporters Na+/Cl– cotransporter (NCC) and Na+/K+/2Cl– cotransporters 1 and 2 (NKCC1 and NKCC2), thus causing the increased intake of sodium, chloride, and potassium. Additionally, the proteins KLHL3 and CUL3 form a complex that binds to WNK4 and breaks it down, thus decreasing the absorption of these electrolytes. Mutations in all these proteins can cause Gordon’s syndrome [R, R, R, R].

2) Bartter’s Syndrome

Bartter’s syndrome is a rare inherited defect of the kidney cells in the part of the kidney that reabsorbs electrolytes (loop of Henle) and is characterized by [R]:

Potassium wasting

Low blood chloride levels

Metabolic alkalosis (high blood pH)

High blood renin levels

High aldosterone secretion

Normal blood pressure

High urine prostaglandin levels

Frequent need to drink and urinate

The syndrome is caused by mutations in the Na+/K+/2Cl– cotransporter 2 (NKCC2), as well as in the following related proteins [R]:

ROMK (a protein that moves potassium out of the cells)

ClC-Kb (a protein that moves chloride out of the cells)

CaSR (a protein that detects calcium levels and uses them as a signal to activate electrolyte transporters)

3) Gitelman’s Syndrome

Gitelman’s syndrome is a hereditary disease with similar symptoms to Bartter’s (metabolic alkalosis with low potassium, low chloride, high renin, and high aldosterone levels in the blood), but due to defects in the kidney cells of a different region (distal convoluted tubule). The condition is caused by mutations in the Na+/Cl– cotransporter (NCCT) [R, R].

4) Cystic Tissue Scarring

Cystic tissue scarring is a hereditary disorder characterized by the following symptoms [R]:

5) Addison’s Disease

Addison’s disease is a rare hereditary disorder in which the glands above the kidneys are defective and produce low levels of the hormones cortisol and aldosterone. The main symptoms of this disorder are [R]:

6) Congenital Chloride Diarrhea

Congenital chloride diarrhea is a rare genetic disease characterized by the production of watery diarrhea with high chloride concentration. It causes dehydration, metabolic alkalosis, and low levels of blood chloride, sodium, and potassium. The condition is due to defects in the bowel chloride and bicarbonate transporter SLC26A3 [R, R].

7) Syndrome of Inappropriate Antidiuresis

This syndrome is characterized by reduced water elimination, continued production or action of the antidiuretic hormone vasopressin, and low blood sodium and chloride levels [R].

The disease is caused by activating mutations in the vasopressin receptor AVPR2, which leads to the excessive accumulation of water [R].

Effect of Drugs on Chloride Levels

1) Carbonic Anhydrase Blockers

Carbonic anhydrase II transforms carbon dioxide into bicarbonate. Blocking this enzyme increases chloride accumulation to compensate for the reduction of negative electrolytes. The main blockers are [R]:

Acetazolamide (used for glaucoma, epilepsy, pressure around the brain, and altitude sickness)

Methazolamide (used for glaucoma and pressure in the eyes)

Ethoxzolamide (used for glaucoma, ulcers in the bowel, and as a diuretic)

Dichlorphenamide (used for glaucoma and as a diuretic)

Dorzolamide (used for glaucoma and pressure in the eyes)

Brinzolamide (used for glaucoma and pressure in the eyes)

Zonisamide (used for epilepsy and Parkinson’s disease)

Some inhibitors of the enzyme that produce prostaglandins during inflammation also inhibit carbonic anhydrase II. Among them, the main ones are [R]:

Celecoxib (arthritis and menstruation and acute pain)

Valdecoxib (arthritis and menstruation pain)

Rofecoxib (arthritis and menstruation pain)

2) Diuretics

Loop diuretics are drugs acting on a certain region of kidney cells (loop of Henle), where they block the Na+/K+/2Cl– cotransporter. As a result, they reduce the reabsorption of sodium, potassium, and chloride in the kidneys. The main ones are [R]:

Furosemide

Bumetanide

Ethacrynic acid

Torsemide

Thiazides and thiazide-like diuretics increase water elimination by blocking the Na+/Cl– cotransporter, which prevents the absorption of sodium and chloride in the kidneys. The most common ones are [R, R]:

Hydrochlorothiazide

Bendroflumethiazide

Metolazone

Chlorthalidone

Clopamide

Xipamide

Potassium-sparing diuretics are drugs that increase the elimination of water, sodium, and chloride through the kidneys without causing potassium losses. The main ones are [R]:

Aldosterone blockers like spironolactone and eplerenone: they prevent the binding of aldosterone (a hormone triggering the production of electrolyte transporters) to its receptor [R].

3) Corticosteroids

Aldosterone is a hormone that promotes sodium and chloride absorption. Corticosteroid drugs such as cortisone and hydrocortisone bind to the aldosterone receptor and also activate the absorption of these electrolytes [R, R].

However, the long-term use of corticosteroid drugs causes a condition called Cushing’s syndrome in which the glands above the kidneys are damaged and the production of aldosterone and other corticosteroid hormones stops. This causes the loss of sodium and chloride [R, R].

4) Laxatives

The laxative lubiprostone turns on the chloride channel ClC-2, which secretes chloride to induce the entry of sodium and water into the bowel. Similarly, a herbal laxative (anthraquinone) turns on the chloride secretion channel CFTR [R, R].

Limitations and Caveats

Although the studies were largely human studies, a large number of them were retrospective cohort studies. Because these studies look at existing data, the data may be inaccurate, incomplete, or inconsistently measured. Thus, most of the data collected is only correlational (shows a relationship between the factors) and not causal (determines a cause and effect) [R].

Irregular Chloride Levels?

If you have not yet tested your chloride levels, I recommend that you ask your doctor to do it. If you already have your blood test results and you’re not sure what to make of them, check out Lab Test Analyzer. It does all the heavy lifting for you. No need to spend thousands of hours researching what to make of your various blood tests.

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It’s super-simple so that even if you don’t have any background in science, you will understand what your results mean and what you can do to get them in the optimal range.

Lab Test Analyzer gives you up-to-date scientific information about your lab results. In addition, you will get both lifestyle tips and natural solutions to help you optimize your health. You can also rely on our science-based optimal ranges to help prevent potential health issues and maximize your overall well-being.

All of the content is backed by science and researched by a team of PhDs, professors, and scientists.

We’re all unique, so we deserve solutions that treat us that way.

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JOE COHEN

CEO, SelfHacked

About Joe

Growing up, Joe was plagued with a myriad of health issues such as gut problems, autoimmune issues, chronic fatigue, brain fog, insomnia, and general inflammation. Both conventional and alternative doctors weren’t able to help him, so he decided to fix himself. With lots of health questions and few satisfying answers, Joe decided to read every research paper he could get his hands on and conduct thousands of experiments on his own body in order to fix his health issues. Joe started SelfHacked in late 2013 when he successfully fixed all of his issues, and now it gets millions of readers a month looking to educate themselves about how they can improve their health. Joe is now a thriving author, speaker, and serial entrepreneur, founding SelfDecode & LabTestAnalyzer.

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